New Progress in Targeted Lung Cancer Therapy

April 19, 2010 (Washington, D.C.) -- New research offers hope that people with lung cancer will live longer if drug therapy is guided by the molecular traits of tumors.

"The goal is to match the correct drug with the right patient, based on the best tumor markers we have," says Roy Herbst, MD, of the University of Texas M.D. Anderson Cancer Center in Houston.

So far, researchers have only shown that so-called targeted drugs seem to shrink tumors better if they are chosen based on tumors' specific molecular traits, or biomarkers.

But there is a hint that these gains will someday translate into living longer, Herbst tells WebMD.

Herbst led the mid-stage trial known as BATTLE, short for Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination. In the study, researchers tested four targeted drugs based on patients' biomarkers.

After eight weeks, tumors shrank or stopped growing in 46% of the patients, all of whom had late-stage lung cancer. Typically, only about 30% of these patients would be expected to respond, Herbst says.

Lung Cancer's Toll

Targeted therapies such as Herceptin and Gleevec have dramatically improved the survival of breast cancer and leukemia patients, but "we're in the dark ages of lung cancer treatment," says M.D. Anderson's Edwin Kim, MD. He presented the BATTLE findings at the annual meeting of the American Association for Cancer Research.

Until recently, there have been few treatment options; with chemotherapy, patients lived an average of only eight months from diagnosis.

In the study, all the patients underwent biopsies so their tissue could be tested for biomarkers associated with non-small-cell lung cancer.

Patients were given one of four targeted treatments: Tarceva, Zactima, Targretin, or Nexavar.

The best results were seen with Nexavar, Kim says. Already approved for liver and kidney cancer, it targets a mutation in a gene called KRAS that is implicated in many cancers.

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Tumors shrank or stopped growing in 61% of patients with KRAS mutations in the study. Surprisingly, 56% of patients with no KRAS mutations were also helped by the drug. "Nexavar may be able to blaze a trail in lung cancer," Kim says.

Tarceva blocks EGFR, a gene that is overactive in many types of cancer cells.

In the study, tumors shrank or stopped growing in 71% of the lung cancer patients with EGFR mutations who were given Tarceva and 34% of those without them.

Zactima and Targretin also worked better for some people whose tumors had specific molecular traits, Kim says.

The drugs had fewer side effects than typically seen with chemotherapy, he says. About 6.5% of patients suffered serious side effects such as collapsed lung.

Learning as They Go

The researchers adopted an unusual study design that they expect will catch on: adapting as they learned. After about 40% of the patients were enrolled, the researchers used what they had learned about which combinations of drug and biomarkers were more likely to result in disease control to refine drug choices for the others.

One finding of the study was that patients whose tumors shrank or stopped growing -- what doctors call disease control -- by eight weeks lived an average of just under one year. Patients who didn't respond by eight weeks lived an average of only seven months.

This means researchers can use disease control to assess whether treatments are working sooner, sparing patients the side effects, expense, and psychological trauma of unnecessary treatment, Kim says.

'Cautious Optimism'

Paul A. Bunn Jr., MD, of the University of Colorado in Denver, expressed cautious optimism.

By definition, data from a mid-stage phase II trial like BATTLE are preliminary, he tells WebMD. And there were only a small number of people with some of the molecular signatures, he says.

There is still a long way to go before this method can be integrated into everyday clinical practice, Bunn says.

Kim agrees. "This is a first step to find biomarkers that may help supplant existing toxic therapies and to find the right population for a particular drug," he says.

Matching the right drug to the right patient will cut down on expenses, he says, as targeted drugs can cost more than $10,000 a year.

Of the drugs used in the trial, only Tarceva is approved to treat lung cancer.

The study was sponsored by the U.S. Department of Defense with support from the National Cancer Institute and some pharmaceutical companies.